Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in philadelphia chromosome positive malaysian chronic myeloid leukemia patients

Marjanu Hikmah Elias, Abdul Aziz Baba, Azlan Husin, Abu Dzarr Abdullah, Rosline Hassan, Goh Ai Sim, S Fadilah S. Abdul Wahid, Ravindran Ankathil

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Development of resistance to imatinib mesylate (IM) in chronic myeloid leukemia (CML) patients is mediated by different mechanisms that can be classified as BCR-ABL dependent or BCR-ABL independent pathways. BCR-ABL dependent mechanisms are most frequently associated with point mutations in tyrosine kinase domain (TKD) of BCR-ABL1 and also with BCR-ABL gene amplification. Many different types and frequencies of mutations have been reported in different studies, probably due to the different composition of study cohorts. Since no reports are available from Malaysia, this study was undertaken to investigate the frequency and pattern of BCRABL kinase domain mutations using dHPLC followed by sequencing, and also status ofBCR-ABL gene amplification using fluorescence in situ hybridization (FISH) on 40 IM resistant Malaysian CML patients. Mutations were detected in 13 patients (32.5%). Five different types of mutations (T315I, E255K, Y253H, M351T, V289F) were identified in these patients. In the remaining 27 IM resistant CML patients, we investigated the contribution made by BCR-ABL gene amplification, but none of these patients showed amplification. It is presumed that the mechanisms of resistance in these 27 patients might be due to BCRABL independent pathways. Different mutations confer different levels of resistance and,therefore, detection and characterization of TKD mutations is highly important in order to guide therapy in CML patients.

Original languageEnglish
Pages (from-to)86-90
Number of pages5
JournalHematology Reports
Volume4
Issue number4
DOIs
Publication statusPublished - 2012
Externally publishedYes

Fingerprint

Philadelphia Chromosome
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Phosphotransferases
Mutation
Gene Amplification
Protein-Tyrosine Kinases
Imatinib Mesylate
Malaysia
Mutation Rate
Fluorescence In Situ Hybridization
Point Mutation
Cohort Studies

Keywords

  • BCR-ABL dependent mechanisms
  • Chronic myeloid leukemia
  • Imatinib mesylate
  • Mutation
  • Tyrosine kinase domain

ASJC Scopus subject areas

  • Hematology

Cite this

Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in philadelphia chromosome positive malaysian chronic myeloid leukemia patients. / Elias, Marjanu Hikmah; Baba, Abdul Aziz; Husin, Azlan; Abdullah, Abu Dzarr; Hassan, Rosline; Sim, Goh Ai; S. Abdul Wahid, S Fadilah; Ankathil, Ravindran.

In: Hematology Reports, Vol. 4, No. 4, 2012, p. 86-90.

Research output: Contribution to journalArticle

Elias, Marjanu Hikmah ; Baba, Abdul Aziz ; Husin, Azlan ; Abdullah, Abu Dzarr ; Hassan, Rosline ; Sim, Goh Ai ; S. Abdul Wahid, S Fadilah ; Ankathil, Ravindran. / Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in philadelphia chromosome positive malaysian chronic myeloid leukemia patients. In: Hematology Reports. 2012 ; Vol. 4, No. 4. pp. 86-90.
@article{71cde2e6330b44b68a1fcaae45809c56,
title = "Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in philadelphia chromosome positive malaysian chronic myeloid leukemia patients",
abstract = "Development of resistance to imatinib mesylate (IM) in chronic myeloid leukemia (CML) patients is mediated by different mechanisms that can be classified as BCR-ABL dependent or BCR-ABL independent pathways. BCR-ABL dependent mechanisms are most frequently associated with point mutations in tyrosine kinase domain (TKD) of BCR-ABL1 and also with BCR-ABL gene amplification. Many different types and frequencies of mutations have been reported in different studies, probably due to the different composition of study cohorts. Since no reports are available from Malaysia, this study was undertaken to investigate the frequency and pattern of BCRABL kinase domain mutations using dHPLC followed by sequencing, and also status ofBCR-ABL gene amplification using fluorescence in situ hybridization (FISH) on 40 IM resistant Malaysian CML patients. Mutations were detected in 13 patients (32.5{\%}). Five different types of mutations (T315I, E255K, Y253H, M351T, V289F) were identified in these patients. In the remaining 27 IM resistant CML patients, we investigated the contribution made by BCR-ABL gene amplification, but none of these patients showed amplification. It is presumed that the mechanisms of resistance in these 27 patients might be due to BCRABL independent pathways. Different mutations confer different levels of resistance and,therefore, detection and characterization of TKD mutations is highly important in order to guide therapy in CML patients.",
keywords = "BCR-ABL dependent mechanisms, Chronic myeloid leukemia, Imatinib mesylate, Mutation, Tyrosine kinase domain",
author = "Elias, {Marjanu Hikmah} and Baba, {Abdul Aziz} and Azlan Husin and Abdullah, {Abu Dzarr} and Rosline Hassan and Sim, {Goh Ai} and {S. Abdul Wahid}, {S Fadilah} and Ravindran Ankathil",
year = "2012",
doi = "10.4081/hr.2012.e23",
language = "English",
volume = "4",
pages = "86--90",
journal = "Hematology Reports",
issn = "2038-8322",
publisher = "PagePress",
number = "4",

}

TY - JOUR

T1 - Contribution of BCR-ABL kinase domain mutations to imatinib mesylate resistance in philadelphia chromosome positive malaysian chronic myeloid leukemia patients

AU - Elias, Marjanu Hikmah

AU - Baba, Abdul Aziz

AU - Husin, Azlan

AU - Abdullah, Abu Dzarr

AU - Hassan, Rosline

AU - Sim, Goh Ai

AU - S. Abdul Wahid, S Fadilah

AU - Ankathil, Ravindran

PY - 2012

Y1 - 2012

N2 - Development of resistance to imatinib mesylate (IM) in chronic myeloid leukemia (CML) patients is mediated by different mechanisms that can be classified as BCR-ABL dependent or BCR-ABL independent pathways. BCR-ABL dependent mechanisms are most frequently associated with point mutations in tyrosine kinase domain (TKD) of BCR-ABL1 and also with BCR-ABL gene amplification. Many different types and frequencies of mutations have been reported in different studies, probably due to the different composition of study cohorts. Since no reports are available from Malaysia, this study was undertaken to investigate the frequency and pattern of BCRABL kinase domain mutations using dHPLC followed by sequencing, and also status ofBCR-ABL gene amplification using fluorescence in situ hybridization (FISH) on 40 IM resistant Malaysian CML patients. Mutations were detected in 13 patients (32.5%). Five different types of mutations (T315I, E255K, Y253H, M351T, V289F) were identified in these patients. In the remaining 27 IM resistant CML patients, we investigated the contribution made by BCR-ABL gene amplification, but none of these patients showed amplification. It is presumed that the mechanisms of resistance in these 27 patients might be due to BCRABL independent pathways. Different mutations confer different levels of resistance and,therefore, detection and characterization of TKD mutations is highly important in order to guide therapy in CML patients.

AB - Development of resistance to imatinib mesylate (IM) in chronic myeloid leukemia (CML) patients is mediated by different mechanisms that can be classified as BCR-ABL dependent or BCR-ABL independent pathways. BCR-ABL dependent mechanisms are most frequently associated with point mutations in tyrosine kinase domain (TKD) of BCR-ABL1 and also with BCR-ABL gene amplification. Many different types and frequencies of mutations have been reported in different studies, probably due to the different composition of study cohorts. Since no reports are available from Malaysia, this study was undertaken to investigate the frequency and pattern of BCRABL kinase domain mutations using dHPLC followed by sequencing, and also status ofBCR-ABL gene amplification using fluorescence in situ hybridization (FISH) on 40 IM resistant Malaysian CML patients. Mutations were detected in 13 patients (32.5%). Five different types of mutations (T315I, E255K, Y253H, M351T, V289F) were identified in these patients. In the remaining 27 IM resistant CML patients, we investigated the contribution made by BCR-ABL gene amplification, but none of these patients showed amplification. It is presumed that the mechanisms of resistance in these 27 patients might be due to BCRABL independent pathways. Different mutations confer different levels of resistance and,therefore, detection and characterization of TKD mutations is highly important in order to guide therapy in CML patients.

KW - BCR-ABL dependent mechanisms

KW - Chronic myeloid leukemia

KW - Imatinib mesylate

KW - Mutation

KW - Tyrosine kinase domain

UR - http://www.scopus.com/inward/record.url?scp=84870326556&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84870326556&partnerID=8YFLogxK

U2 - 10.4081/hr.2012.e23

DO - 10.4081/hr.2012.e23

M3 - Article

C2 - 23355941

AN - SCOPUS:84870326556

VL - 4

SP - 86

EP - 90

JO - Hematology Reports

JF - Hematology Reports

SN - 2038-8322

IS - 4

ER -